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A3.15 Reconstituted High Density Lipoprotein (rHDL) Modulates T Effector Cell Function in a Murine Model of Rheumatoid Arthritis
  1. I Tiniakou1,2,
  2. VI Zannis1,4,
  3. D Boumpas3,
  4. P Verginis*,3,
  5. D Kardassis*,1,2
  1. 1University of Crete Medical School, Heraklion, Greece
  2. 2Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology of Hellas, Heraklion, Greece
  3. 3Biomedical Research Foundation of the Academy of Athens, Greece
  4. 4Boston University Medical Center, Boston, USA

Abstract

Background and Objectives High density lipoprotein (HDL) has a variety of functions which confer protection from cardiovascular and other human diseases. Increased cardiovascular risk is observed in humans with autoimmune disorders such as rheumatoid arthritis (RA), which is associated with either low levels or dysfunctional HDL. Recent evidence suggests a role of HDL in modulating both innate and adaptive immune responses. We sought to investigate the role of rHDL during the development of an autoimmune response in the antigen-induced arthritis (AIA) mouse model.

Materials and Methods C57BL/6 mice were subcutaneously immunised with ovalbumin (OVA) in complete Freund’s adjuvant (CFA) and the inguinal lymph nodes (LN) were excised 9 days after the antigenic challenge. The LN cells were cultured in vitro in the presence of varying concentrations of reconstituted HDL (rHDL) in the presence or absence of OVA and OVA-specific immune responses were measured. To assess the effect of HDL on dendritic cell activation and maturation, mouse bone marrow was cultured with GM-CSF to generate dendritic cells (BM-DCs), which were collected, cultured and treated with LPS in the presence or absence of rHDL.

Results OVA-primed LN cells secreted increased levels of IFN-γ and IL-17 that were significantly suppressed in the presence of rHDL in a dose-dependent manner. rHDL was also found to exert a suppressive effect on T cell proliferation as indicated by IL-2 measur- ement. Finally, rHDL-treated LPS-stimulated BM-DCs did not demonstrate any significant phenotypic differences as assessed by FACS analysis on CD86, CD40 and PDL-1 molecules as compared to control LPS-stimulated BM-DCs.

Conclusions rHDL exerts a direct immunomodulatory function on T cells in vitro by suppressing their proliferation and the expression of inflammatory cytokines. Ongoing work is focused on the delineation of the mechanism involved in the rHDL-mediated suppression of the immune response both in vitro and in vivo. These data identify rHDL as an important player in the homeostatic regulation of the inflammatory response and a potential therapeutic target for chronic inflammatory diseases.

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